title: Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients.
abstract: Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognized by CD4(+) T cells. The aim of this study was to evaluate the extent of cancer-immune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4(+) T cell immunity. CD4(+) T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4(+) T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4(+) T cells from normal donors produced mainly GM-CSF and IFN-gamma, CD4(+) T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4(+) T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3(+) compared with T-bet(+) lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.
authors.affiliation: Tumor Immunology Unit, Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tassi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gavazzi
authors.forename: Luca
authors.initials: L
authors.lastname: Albarello
authors.forename: Vladimir
authors.initials: V
authors.lastname: Senyukov
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Marco
authors.initials: M
authors.lastname: Braga
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Carlo
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Protti
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000276:immunology*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008979:Moloney murine leukemia virus / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D002272:Carcinoembryonic Antigen; C402641:EBNA-2 protein, Human herpesvirus 4; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins